Citrulline is one kind of amino acid which is not used as a synthetic starting material of protein and present as a free form in the body. In the body, it plays an important role as an arginine precursor for biosynthesis of arginine or as a constituent factor of NO cycle involved in the supply of nitric oxide (NO).
Citrulline has been reported to have a vasodilating action since it shows a relaxation action on the vascular smooth muscle of rabbit (non-patent document 1). It is said to have various other effects such as suppression of arteriosclerosis, improvement of cold feeling, energy enhancement, ammonia detoxification and the like.
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) and dihydrocapsaicin (8-methyl-N-vanillyl-nonanamide) are pungent taste components contained in chili pepper. They have long been used as a spice for foods, and a counterirritant for medical treatments. In addition, they have physiological activities such as promotion of appetite, analgesic action and the like. In recent years, it has been reported that administration of capsaicin activates TRPV1 (Transient Receptor Potential Vanilloid 1), enhances endothelial-dependent vascular relaxation and prevents hypertension (non-patent document 2).
Capsaicin is known to have a strong pungent taste and irritant property. According to a study relating to a sublingual treatment with a capsaicin solution, irritant saliva secretion due to capsaicin is promoted in a concentration-dependent manner, and when the concentration of capsaicin solution is not less than 75 μM, a feeling of strong pain was produced in a concentration-dependent manner (non-patent document 3). Thus, use of capsaicin for foods and pharmaceutical products is limited due to its strong pungent taste, irritant property and poor solubility.
The concentration range of capsaicin that does not stimulate animal tissues is not more than several dozen μM and, as mentioned above, while the development of a method of effectively potentiating action by a combination of capsaicin in a low concentration range free of irritant property and known material is useful but has not been known heretofore.